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The second of four children, Australian native Melissa George was born in Perth, Western Australia in 1976. The daughter of a nurse and a construction worker, George initially expressed interest in various forms of dance rather than acting. During her childhood, George studied tap, ballet, and jazz, later transitioning into professional rollerskating - similar to figure skating on ice.

By age 16, George had won several awards at various National Rollerskating Championships in Australia, and subsequently began modeling after dropping out of high school. George met a casting agent while doing modeling work, and was given a role on the popular Australian soap opera "Home and Away" (1988); George moved to Sydney and worked on the show for three years until deciding to pursue other projects.

In 1996, George left Australia and moved to Los Angeles in search of bigger roles. She garnered various supporting parts in films such as Dark City (1998) and Steven Soderbergh's crime thriller The Limey (1999), before landing a key part in David Lynch's acclaimed neo noir mystery film, Mulholland Dr. (2001). While in Bali in 1998, George met future husband, Chilean filmmaker Claudio Dabed; the two were married in late 2000.

The early 2000s would have George playing bit parts in several American television shows, including "Friends" (1994) and "Monk" (2002), ultimately landing a recurring role on the hit "Alias" (2001) alongside Jennifer Garner and Michael Vartan. Through the later part of the decade, George had roles in various horror and thriller films, beginning with the 2005 version of The Amityville Horror (2005), as well as the commercially-successful thriller Derailed (2005/I) alongside Clive Owen, Jennifer Aniston and Vincent Cassel.

George finished the decade with several more horror films, including Turistas (2006) and 30 Days of Night (2007), as well as independent horror titles such as w Delta z (2007), The Betrayed (2008) and Triangle (2009). George was also active in television work, landing a role on the popular medical drama "Grey's Anatomy" (2005). Her greatest critical success would come with a role on "In Treatment" (2008), playing the love interest of Gabriel Byrne, which would garner her a Golden Globe nomination in 2009.

Though a veteran of television in both Australia and the United States, George has achieved considerable success in her film career, which has hardly spanned over a decade.